The psychological burden associated with metabolic syndrome: Evidence from UK and US older adults

Abstract Introduction We examined the psychological burden associated with metabolic syndrome (MetSyn). Methods We used comparable longitudinal data of older adults (≥50 years) from the UK (English Longitudinal Study of Aging) and the US (Health and Retirement Study). We defined MetSyn based on biomarker assessments (e.g., blood pressure, impaired glycemic control). Using regression models, we tested a range of individual psychological outcomes (e.g., depressive symptoms) associated with MetSyn. We also examined whether these psychological outcomes may explain or moderate the link between MetSyn and non‐communicable diseases (NCDs). Findings MetSyn was associated cross‐sectionally with a range of psychological outcomes, including depression, anxiety, loneliness, hopelessness, cynical hostility, social strain, negative affect and decreased positive affect, social support and purpose in life. There was no convincing evidence that psychological factors interacted with or explained (mediated) the relationship between MetSyn and increased risk of developing NCD over 10‐year follow‐ups. Conclusions MetSyn and the psychological burden outcomes examined may have independent effects on NCD risk.


| INTRODUCTION
Metabolic syndrome (MetSyn) is a well establish risk factor for development of non-communicable diseases (NCDs), such as heart disease and stroke. 1,2Conceptually related to MetSyn is obesity and there is a sizable psychosocial burden associated with obesity that is thought to detrimentally impact the management of obesity and obesity-related health outcomes. 3Like obesity, MetSyn has also been shown to be associated with worse mental health, including increased depression and anxiety symptoms. 4,5However, the association MetSyn has with a wider range of psychological factors that can shape physical health outcomes is unclear. 6In particular, there is limited research examining how MetSyn relates to other markers of mental health (e.g., experiences of positive affect) and psychosocial factors such as social support or loneliness, in the general population. 7Moreover, it is important to understand if MetSyn is associated with worse mental health and psychosocial factors, independent of obesity status, as MetSyn has become relatively common in adults in This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
the normal weight and overweight BMI range. 8Therefore, in the present research, we examined the association that MetSyn has with a wide range of health-relevant psychosocial factors, independent to obesity status, among samples of nationally representative UK and US older adults.
Until now, it has been widely assumed that MetSyn increases the risk of ill physical health due to the direct physiological impact MetSyn has on the body (e.g., dysregulation of metabolic functioning, inflammation). 1 Yet, the psychological burden associated with MetSyn may be important as it could interact with MetSyn (moderation), with those experiencing negative psychological effects of MetSyn being at amplified risk of NCD development.For example, a study of employed US adults found that worse mental health (stress and anxiety) among male participants with MetSyn was associated with increased blood pressure, but no such relationship was observed among participants without MetSyn. 9These findings are consistent with the proposition that worse mental health may amplify the damaging effects that MetSyn has on physical health, but there has been limited additional testing of this proposition in the context of disease development.
Alternatively, it is possible that the psychological burden associated with MetSyn may in part explain (mediation) how MetSyn increases the risk of NCD development, as negative psychological factors have been shown to contribute to poorer physiological health.
Individuals living with MetSyn experience worse psychological wellbeing, 10 and impairments in psychological well-being are risk factors for NCD development. 11,12Therefore, a currently untested proposition is that impaired psychological well-being may be partially responsible for why NCD development is more common among those living with MetSyn.Although we are aware of no research directly testing this possibility using longitudinal cohort data, there is a significant body of related research which proposes that the psychological burden of obesity may explain why obesity is associated with worse physical health. 13better conceptualization of the psychological burden associated with MetSyn and whether this burden may contribute to adverse physical health outcomes among those living with MetSyn may provide insights for MetSyn management and treatment provision. 14Therefore, the present research examined whether psychological factors have any moderating or mediating MetSyn-related NCD development risk in later life, as opposed to an independent (additive) effect.

| English Longitudinal Study of Aging (ELSA)
English Longitudinal Study of Aging (ELSA) is a representative longitudinal study of older English adults (≥50 years). 15

| Health and Retirement Study (HRS)
Health and Retirement Study (HRS) is a comparable study of older US adults. 16For the present study, data were combined from Waves 9

| Psychological measures
Both ELSA and HRS included validated measures of depressive symptoms, life satisfaction, loneliness, social support and social strain.Eudemonic well-being and enjoyment of life were measured in ELSA only, and positive and negative affects, purpose in life, anxiety, hopelessness, optimism, pessimism, cynical hostility, personal constraint and mastery were assessed in the HRS only.See Supporting Information S1 for detailed measurement information.We followed our previous approach in quantifying these psychological outcomes. 18All measures that were on a continuous scale were standardized using the z-score method to enable comparison across different metrics.

| Non-communicable disease (NCDs)
In both studies, the risk of participants developing heart disease, stroke, arthritis, cancer and cognitive decline (memory-related disease) was examined.Diabetes or hypertension were not examined as MetSyn classification was dependent on diagnostic factors.Health conditions were measured via self-reported doctor diagnosis ("Has a doctor ever told you that you have…?"), with the exception of cognitive decline that was also measured via a telephone interview test for cognitive status (as in 18 ).See Supporting Information S1 for full details.

| Analyses
Linear regressions tested the association between MetSyn and each psychological measure at baseline, controlling for covariates (see above).Associations were also examined with a composite measure of psychological measures that loaded onto single factors relating to "Psychological Distress" (see Table 1 T A B L E 1 Cross-sectional associations between metabolic syndrome status and psychological measures.The association between metabolic syndrome and psychological outcomes was examined in separate regression models for each outcome and controlled for age, sex, ethnicity, marital status, employment status, education (degree qualification in ELSA, the number of years in education in HRS), household wealth, and BMI category.Using exploratory factor analysis, psychological measures loaded onto the same underlying single factor, defined as having an item loading factor ≥0.55 (good item loading), were combined into a composite index of psychological distress separately in each study (as in 18 ).Index of psychological distress was developed by re-standardizing the average standardized scores of 5 psychological measures in ELSA (depressive symptoms, eudemonic wellbeing, enjoyment of life, life satisfaction, loneliness) and 10 psychological measures in HRS (depressive symptoms, life satisfaction, loneliness, positive affect, negative affect, purpose in life, anxiety, hopelessness, pessimism, and personal constraint) that were found to load onto a single factor in factor analysis.
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-3 of 9 ELSA (54% female, 66 mean years old) and HRS (55% female, 66 mean years old) were comparable for basic demographics.MetSyn was common in the UK (60%) and US (52%) at baseline.See online Supporting Information S1 for detailed participant characteristics.As indicated in Table 1, MetSyn (vs.its absence) was cross -sectionally associated with a wide range of negative psychosocial outcomes, including increased depression, anxiety, loneliness, hopelessness, cynical hostility, social strain, negative affect and decreased positive affect, social support and purpose in life.In HRS, MetSyn was significantly associated with reduced life satisfaction (but not in ELSA).MetSyn (vs.its absence) was associated with significantly raised levels of psychological distress on the overall composite index in both ELSA (β = 0.12, 95% CI: 0.06-0.18)and HRS (β = 0.11, 95% CI: 0.06-0.016).
MetSyn status at baseline was associated with increased risk of developing stroke in both ELSA and HRS (hazard ratios ranging from 1.45 to 1.57), heart disease in HRS (HR = 1.32), arthritis in ELSA (HR = 1.21), but not cancer or cognitive decline in both studies (hazard ratios ranging from 0.19 to 1.05).See Tables 2 and 3.There was no evidence that any psychological measures (independently or when combined in composite) significantly moderated or mediated the associations between MetSyn status at baseline and NCD development.See Tables 4 and 5 for moderation analyses in full and online supplementary materials for mediation results.

| DISCUSSION
Across two large nationally representative studies of UK and US older adults, there was convincing evidence that MetSyn was associated with a considerable psychological burden.These findings replicate previous research identifying cross-sectional relationships between MetSyn and both depression and anxiety. 5,17In addition, MetSyn was associated with a range of other negative psychosocial factors, including hopelessness, cynical hostility, increased negative affect, decreased positive affect, social support and purpose in life. 19,20Unlike in previous research, a global approach to considering the psychological burden associated with MetSyn was adopted by examining how MetSyn is related to a wide range of psychological factors.The present findings suggest that MetSyn is characterized by a clustering of numerous negative psychological variables including mental health (e.g., anxiety, depression), life outlook (e.g., purpose in life, pessimism) and social (e.g., perceived social support and social strain) factors.An implication of these findings is that the considerable psychological burden associated with MetSyn would benefit from being addressed (e.g., through access to psychological therapies) and/or considered in the clinical management and treatment of patients with MetSyn.T A B L E 4 Two-way interaction terms between metabolic syndrome status and psychological measures at baseline in the development of subsequent non-communicable health conditions in ELSA.As expected, MetSyn was predictive of an increased risk of developing heart disease and stroke. 1 However, there was no convincing evidence that the increased risk of developing NCDs associated with MetSyn was reliably moderated or mediated by psychological factors.Based on these findings, MetSyn and its associated psychological burden are therefore likely to have independent and additive effects on NCD risk, as opposed to psychological factors explaining why MetSyn increases NCD development risk.These findings are consistent with other research using HRS and ELSA, which suggests that the direct relationship between obesity and NCD risk is also not explained by people with obesity having lower psychological well-being than people without obesity. 18mitations of the present work are that findings may not generalize to younger adults and due to available data, definitions of MetSyn differed between UK and US samples.However, the results were comparable between the two.Future research will benefit from better understanding why psychosocial measures are associated with MetSyn, as it is feasible that they may predispose individuals to the development of MetSyn and/or be a direct consequence of MetSyn.These limitations notwithstanding, the present study findings highlight the need to monitor and intervene to improve psychosocial well-being among individuals living with MetSyn.Related to this, future research may benefit from examining how the psychological burden associated with MetSyn impacts management and treatment outcomes associated with MetSyn. 21 Wave 4 (2008-2009) acted as the cross-sectional baseline in this study due to the range of psychological measures available.Development of NCDs was examined from baseline up to Wave 9 (2018-2019), including biennial measurement at Waves 5 (2010-2011), 6 (2012-2013), 7 (2014-2015), and 8 (2016-2017).
, five measures in ELSA, 10 measures in HRS).Cox-proportional hazard regression models examined how MetSyn at baseline related to new diagnosis for each NCD (covariates included).Time to diagnosis was calculated from the date of the interview at baseline to the diagnosis date/follow-up interview when the NCD was first reported.Participants with the NCDs of interest at baseline were excluded per model.Interaction terms were included between MetSyn status and each psychological measure to test evidence for moderation.Causal mediation analysis was used to examine the role of any psychological measures in explaining the association between MetSyn and NCDs.Inverse probability weighting accounted for loss to follow-up (see Supporting Information S1 for full information).To account for the large number of analyses conducted, alpha was reduced to <0.01 for mediation and moderation analyses.The analyses were pre-registered at https://doi.org/10.17605/OSF.IO/JRQAP, with the exception of moderation analyses (unplanned additional analysis).

Metabolic syndrome (yes vs. no)*psychological measures n HR 95% CI
The association was adjusted for age, sex, ethnicity, marital status, paid employment status, completion of degree qualification level, household wealth, and BMI category.Index of psychological distress was developed by re-standardizing the average standardized scores of 5 psychological measures (depressive symptoms, eudemonic wellbeing, enjoyment of life, life satisfaction, loneliness) that were found to load onto a single factor in factor analysis.Two-way interaction terms between metabolic syndrome status and psychological measures at baseline in the development of subsequent non-communicable health conditions in HRS.
-ROBINSON ET AL.T A B L E 5 (Continued) Interaction:

Metabolic syndrome (yes vs. no)*psychological measures n HR 95% CI
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